1. Field of the Invention
This invention relates generally to new polypeptide fractions, their methods of isolation, biological actions of the peptides, and therapeutic usefulness. More particularly, the present invention relates to new polypeptide fractions isolated from the lungs of animals, and more particularly from the lungs of hogs by novel purification procedures, and to the wide-range of biological activities of the polypeptides.
2. Description of the Prior Art
It is well-known that polypeptide hormones regulate many physiologic functions and mediate certain pathological responses. While numerous compounds have been known to possess a vasodilator effect, many possess this effect only to a relatively slight degree or for a very short time. Medical science has, therefore, sought materials exhibiting a more potent or sustained vasodilator effect which would be more useful therapeutic agents.
In Prior U.S. Pat. Nos. 3,879,371, 3,880,826, 3,862,927 and 3,898,329 of the present inventors, there is disclosed a vasoactive peptide and its method of isolation from the upper intestinal wall of porcine. The porcine vasoactive intestinal peptide was identified as an octacosapeptide of specific sequence which exhibited biological activity in the areas of systemic vasodilation, hypotension, increased cardiac output, respiratory stimulation and hyperglycemia. A report on this peptide and its method of isolation may be found in the literature in Science, pps. 169, 1217-1218 (1970). Another publication of interest to the porcine vasoactive peptide may be found in Eur. J. Biochem., pp. 42, (1974).
The present inventors have previously published articles covering their earlier work regarding peptides present in lung tissue which exhibited vasodilator effects. Thus, in The Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 24, Suppl. 107, pp. 51--56 (1969), it was reported that a peptide fraction had been obtained from lung tissue of hogs which had prolonged peripheral vasodilator activity. Also, in Nature, Vol. 224, No. 5220, pp. 699-700, (1969), there was reported the occurrence in lung tissue of normal hogs, the presence of a vasoactive peptide having a prolonged systemic vasodilator effect. This peptide is indicated as being extractable in a relatively purified form. In the publication Chemistry and Biology of Peptides, pp. 409-414, (1972), the present inventors reported that efforts to isolate a vasoactive polypeptide from hog lungs had led to the extraction and partial purification of two biologically active peptide fractions which are dilators of peripheral systemic and pulmonary vessels, and have activity on non-vascular smooth muscle.
The present invention is concerned with highly purified vasoactive polypeptide fractions which have been isolated from the lungs of animals such as hogs and which exhibit biological activity in inducing peripheral vasodilation and systemic hypotension.